Submit to Toxins Review for Toxins Propose a Special Issue

Journal Menu

Journal Browser

► Journal Browser

Scorpion Toxins

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: closed (31 March 2018) | Viewed by 55601

Share This Special Issue

Special Issue Editor

Prof. Elisabeth Ferroni Schwartz

E-Mail
Guest Editor

Laboratório de Neurofarmacologia, Departamento de Ciências Fisiológicas - bloco G, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, 70910-900, DF, Brasil
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Venoms from scorpions are known to possess a wide variety of potential components for the development of new drugs, as well as insecticides. These molecules appear to have evolved primarily for subjugating prey and for chemical defense, resulting in high degrees of potency and specificity particularly for key signaling molecules in the nervous system. Scorpion toxins, which specifically interfere with ionic channels functioning, have been characterized so far. In addition to these disulfide-bridged peptides, scorpion venoms contain a great diversity of non-disulfide-bridged peptides presenting antimicrobial, immunomodulatory, hypotensive, and antitumoral activities.

This Special Issue of Toxins will cover recent developments relating to scorpion toxins, including evolution, mechanism of action, structure-function, as well as, development or application of screening methods for scorpion toxins, and use and/or development of antivenoms against scorpion toxins.

The individual articles will review:

1. Proteomic analysis of scorpion venom
2. Transcriptomic analysis of venomous glands of scorpions
3. Peptides affecting Ion-channel function
4. Non-disulfide-bridged peptides peptides
5. Antivenoms against scorpion toxins
6. Immunomodulatory activity of scorpion venom toxins
7. Pharmacokinetics, and pharmacodynamics of scorpion toxins

Prof. Elisabeth Ferroni Schwartz
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

K⁺-channel blockers
Na⁺-channel modulators
Cl^--channel toxins
Ca²⁺-channel toxins
Antimicrobial peptides
Defensins
Antitumoral peptides
AMPs
Antivenoms
Immunomodulatory

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (10 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

25 pages, 4127 KiB

Open AccessArticle

Transcriptomic and Proteomic Analyses Reveal the Diversity of Venom Components from the Vaejovid Scorpion Serradigitus gertschi

by Maria Teresa Romero-Gutiérrez, Carlos Eduardo Santibáñez-López, Juana María Jiménez-Vargas, Cesar Vicente Ferreira Batista, Ernesto Ortiz and Lourival Domingos Possani

Toxins 2018, 10(9), 359; https://doi.org/10.3390/toxins10090359 - 5 Sep 2018

Cited by 30 | Viewed by 5988

Abstract

To understand the diversity of scorpion venom, RNA from venomous glands from a sawfinger scorpion, Serradigitus gertschi, of the family Vaejovidae, was extracted and used for transcriptomic analysis. A total of 84,835 transcripts were assembled after Illumina sequencing. From those, 119 transcripts were annotated and found to putatively code for peptides or proteins that share sequence similarities with the previously reported venom components of other species. In accordance with sequence similarity, the transcripts were classified as potentially coding for 37 ion channel toxins; 17 host defense peptides; 28 enzymes, including phospholipases, hyaluronidases, metalloproteases, and serine proteases; nine protease inhibitor-like peptides; 10 peptides of the cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 protein superfamily; seven La1-like peptides; and 11 sequences classified as “other venom components”. A mass fingerprint performed by mass spectrometry identified 204 components with molecular masses varying from 444.26 Da to 12,432.80 Da, plus several higher molecular weight proteins whose precise masses were not determined. The LC-MS/MS analysis of a tryptic digestion of the soluble venom resulted in the de novo determination of 16,840 peptide sequences, 24 of which matched sequences predicted from the translated transcriptome. The database presented here increases our general knowledge of the biodiversity of venom components from neglected non-buthid scorpions. Full article

(This article belongs to the Special Issue Scorpion Toxins)

► Show Figures

Graphical abstract

17 pages, 2635 KiB

Open AccessFeature PaperArticle

Subtype Specificity of β-Toxin Tf1a from Tityus fasciolatus in Voltage Gated Sodium Channels

by Daniel Oliveira da Mata, Diogo Vieira Tibery, Leandro Ambrósio Campos, Thalita Soares Camargos, Steve Peigneur, Jan Tytgat and Elisabeth Ferroni Schwartz

Toxins 2018, 10(9), 339; https://doi.org/10.3390/toxins10090339 - 22 Aug 2018

Cited by 4 | Viewed by 3637

Abstract

Scorpion venoms are a complex mixture of components. Among them the most important are peptides, which presents the capacity to interact and modulate several ion channel subtypes, including voltage-gated sodium channels (Na_V). Screening the activity of scorpion toxins on different subtypes of Na_V reveals the scope of modulatory activity and, in most cases, low channel selectivity. Until now there are approximately 60 scorpion toxins experimentally assayed on Na_V channels. However, the molecular bases of interaction between scorpion toxins and Na_V channels are not fully elucidated. The activity description of new scorpion toxins is crucial to enhance the predictive strength of the structural–function correlations of these Na_V modulatory molecules. In the present work a new scorpion toxin (Tf1a) was purified from Tityus fasciolatus venom by RP-HPLC, and characterized using electrophysiological experiments on different types of voltage-gated sodium channels. Tf1a was able to modify the normal function of Na_V tested, showing to be a typical β-NaScTx. Tf1a also demonstrated an unusual capability to alter the kinetics of Na_V1.5. Full article

(This article belongs to the Special Issue Scorpion Toxins)

► Show Figures

Figure 1

16 pages, 1504 KiB

Open AccessArticle

Tb II-I, a Fraction Isolated from Tityus bahiensis Scorpion Venom, Alters Cytokines’: Level and Induces Seizures When Intrahippocampally Injected in Rats

by Emidio Beraldo Neto, Douglas O. C. Mariano, Lucas A. Freitas, Ana L. C. Dorce, Adriana N. Martins, Daniel C. Pimenta, Fernanda C. V. Portaro, Daniela Cajado-Carvalho, Valquiria A. C. Dorce and Ana L. A. Nencioni

Toxins 2018, 10(6), 250; https://doi.org/10.3390/toxins10060250 - 19 Jun 2018

Cited by 12 | Viewed by 4209

Abstract

Scorpion venoms are composed of several substances with different pharmacological activities. Neurotoxins exert their effects by targeting ion channels resulting in toxic effects to mammals, insects and crustaceans. Tb II-I, a fraction isolated from Tityus bahiensis scorpion venom, was investigated for its ability to induce neurological and immune-inflammatory effects. Two putative β-sodium channel toxins were identified in this fraction, Tb2 II and Tb 4, the latter having been completely sequenced by mass spectrometry. Male Wistar rats, stereotaxically implanted with intrahippocampal cannulas and electrodes, were injected with Tb II-I (2 µg/2 µL) via the intrahippocampal route. The behavior, electrographic activity and cellular integrity of the animals were analyzed and the intracerebral level of cytokines determined. Tb II-I injection induced seizures and damage in the hippocampus. These alterations were correlated with the changes in the level of the cytokines tumoral necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Therefore, the binding of Tb II-I to its target in the central nervous system may induce inflammation resulting in neuropathological and behavioral alterations. Full article

(This article belongs to the Special Issue Scorpion Toxins)

► Show Figures

Figure 1

8 pages, 1593 KiB

Open AccessArticle

Loop Replacement Enhances the Ancestral Antibacterial Function of a Bifunctional Scorpion Toxin

by Shangfei Zhang, Bin Gao, Xueli Wang and Shunyi Zhu

Toxins 2018, 10(6), 227; https://doi.org/10.3390/toxins10060227 - 4 Jun 2018

Cited by 3 | Viewed by 3466

Abstract

On the basis of the evolutionary relationship between scorpion toxins targeting K⁺ channels (KTxs) and antibacterial defensins (Zhu S., Peigneur S., Gao B., Umetsu Y., Ohki S., Tytgat J. Experimental conversion of a defensin into a neurotoxin: Implications for origin of toxic function. Mol. Biol. Evol. 2014, 31, 546–559), we performed protein engineering experiments to modify a bifunctional KTx (i.e., weak inhibitory activities on both K⁺ channels and bacteria) via substituting its carboxyl loop with the structurally equivalent loop of contemporary defensins. As expected, the engineered peptide (named MeuTXKα3-KFGGI) remarkably improved the antibacterial activity, particularly on some Gram-positive bacteria, including several antibiotic-resistant opportunistic pathogens. Compared with the unmodified toxin, its antibacterial spectrum also enlarged. Our work provides a new method to enhance the antibacterial activity of bifunctional scorpion venom peptides, which might be useful in engineering other proteins with an ancestral activity. Full article

(This article belongs to the Special Issue Scorpion Toxins)

► Show Figures

Figure 1

13 pages, 2237 KiB

Open AccessArticle

Antimicrobial and Chemotactic Activity of Scorpion-Derived Peptide, ToAP2, against Mycobacterium massiliensis

by Lázaro M. Marques-Neto, Monalisa M. Trentini, Rogério C. Das Neves, Danilo P. Resende, Victor O. Procopio, Adeliane C. Da Costa, André Kipnis, Márcia R. Mortari, Elisabeth F. Schwartz and Ana Paula Junqueira-Kipnis

Toxins 2018, 10(6), 219; https://doi.org/10.3390/toxins10060219 - 30 May 2018

Cited by 25 | Viewed by 5133

Abstract

Mycobacterium massiliense is a rapid growing, multidrug-resistant, non-tuberculous mycobacteria that is responsible for a wide spectrum of skin and soft tissue infections, as well as other organs, such as the lungs. Antimicrobial peptides had been described as broad-spectrum antimicrobial, chemotactic, and immunomodulator molecules. In this study we evaluated an antimicrobial peptide derived from scorpion Tityus obscurus as an anti-mycobacterial agent in vitro and in vivo. Bioinformatics analyses demonstrated that the peptide ToAP2 have a conserved region similar to several membrane proteins, as well as mouse cathelicidin. ToAP2 inhibited the growth of four M. massiliense strains (GO01, GO06, GO08, and CRM0020) at a minimal bactericidal concentration (MBC) of 200 µM. MBC concentration used to treat infected macrophages was able to inhibit 50% of the bacterial growth of all strains. ToAP2 treatment of infected mice with bacilli reduced the bacterial load in the liver, lung, and spleen, similarly to clarithromycin levels (90%). ToAP2 alone recruited monocytes (F4/80^low Gr1), neutrophils (F4/80⁻ Gr1), and eosinophils (F4/80+ Gr1+). ToAP2, together with M. massiliense infection, was able to increase F4/80^low and reduce the percentage of F4/80^high macrophages when compared with infected and untreated mice. ToAP2 has in vitro anti-microbial activity that is improved in vivo due to chemotactic activity. Full article

(This article belongs to the Special Issue Scorpion Toxins)

► Show Figures

Graphical abstract

16 pages, 10656 KiB

Open AccessArticle

Analogs of the Scorpion Venom Peptide Stigmurin: Structural Assessment, Toxicity, and Increased Antimicrobial Activity

by Adriana M. S. Parente, Alessandra Daniele-Silva, Allanny A. Furtado, Menilla A. Melo, Ariane F. Lacerda, Moacir Queiroz, Cláudia Moreno, Elizabeth Santos, Hugo A. O. Rocha, Euzébio G. Barbosa, Eneas Carvalho, Arnobio A. Silva-Júnior, Marcelo S. Silva and Matheus De F. Fernandes-Pedrosa

Toxins 2018, 10(4), 161; https://doi.org/10.3390/toxins10040161 - 18 Apr 2018

Cited by 37 | Viewed by 6519

Abstract

Scorpion venom is a rich source of biologically active components and various peptides with high-potential therapeutic use that have been characterized for their antimicrobial and antiproliferative activities. Stigmurin is a peptide identified from the Tityus stigmurus venom gland with high antibacterial and antiproliferative activities and low toxicity. Amino acid substitutions in peptides without a disulfide bridge sequence have been made with the aim of reducing their toxicity and increasing their biological activities. The purpose of this study was to evaluate the structural conformation and structural stability, as well as antimicrobial, antiproliferative, and hemolytic activities of two peptide analogs to Stigmurin, denominated StigA6 and StigA16. In silico analysis revealed the α-helix structure for both analog peptides, which was confirmed by circular dichroism. Data showed that the net charge and hydrophobic moment of the analog peptides were higher than those for Stigmurin, which can explain the increase in antimicrobial activity presented by them. Both analog peptides exhibited activity on cancerous cells similar to the native peptide; however, they were less toxic when tested on the normal cell line. These results reveal a potential biotechnological application of the analog peptides StigA6 and StigA16 as prototypes to new therapeutic agents. Full article

(This article belongs to the Special Issue Scorpion Toxins)

► Show Figures

Figure 1

2939 KiB

Open AccessArticle

A Deeper Examination of Thorellius atrox Scorpion Venom Components with Omic Technologies

by Teresa Romero-Gutierrez, Esteban Peguero-Sanchez, Miguel A. Cevallos, Cesar V. F. Batista, Ernesto Ortiz and Lourival D. Possani

Toxins 2017, 9(12), 399; https://doi.org/10.3390/toxins9120399 - 12 Dec 2017

Cited by 34 | Viewed by 6651

Abstract

This communication reports a further examination of venom gland transcripts and venom composition of the Mexican scorpion Thorellius atrox using RNA-seq and tandem mass spectrometry. The RNA-seq, which was performed with the Illumina protocol, yielded more than 20,000 assembled transcripts. Following a database search and annotation strategy, 160 transcripts were identified, potentially coding for venom components. A novel sequence was identified that potentially codes for a peptide with similarity to spider ω-agatoxins, which act on voltage-gated calcium channels, not known before to exist in scorpion venoms. Analogous transcripts were found in other scorpion species. They could represent members of a new scorpion toxin family, here named omegascorpins. The mass fingerprint by LC-MS identified 135 individual venom components, five of which matched with the theoretical masses of putative peptides translated from the transcriptome. The LC-MS/MS de novo sequencing allowed to reconstruct and identify 42 proteins encoded by assembled transcripts, thus validating the transcriptome analysis. Earlier studies conducted with this scorpion venom permitted the identification of only twenty putative venom components. The present work performed with more powerful and modern omic technologies demonstrates the capacity of accomplishing a deeper characterization of scorpion venom components and the identification of novel molecules with potential applications in biomedicine and the study of ion channel physiology. Full article

(This article belongs to the Special Issue Scorpion Toxins)

► Show Figures

Figure 1

7204 KiB

Open AccessArticle

Investigation of Binding Modes and Functional Surface of Scorpion Toxins ANEP to Sodium Channels 1.7

by Yongbo Song, Zeyu Liu, Qi Zhang, Chunming Li, Wei Jin, Lili Liu, Jianye Zhang and Jinghai Zhang

Toxins 2017, 9(12), 387; https://doi.org/10.3390/toxins9120387 - 29 Nov 2017

Cited by 11 | Viewed by 5007

Abstract

The depressant β toxin anti-neuroexcitation peptide (ANEP) from the Chinese scorpion Buthus martensii Karsch has analgesic activity by interacting with receptor site 4 of the voltage-gated sodium channels (VGSCs). Here, with molecular dynamics simulations, we examined the binding modes between ANEP and the site 4 of mice sodium channel 1.7 (mNa_v1.7), a subtype of VGSCs related to peripheral pain. Homology modeling, molecular mechanics, and molecular dynamics in the biomembrane environment were adopted. The results suggested that ANEP bound to the resting site 4 mainly by amino acid residues in the β2–β3 loop and the ‘NC’ domains, and the activate site 4 mainly by amino acid residues in the hydrophobic domain of N-groove and residues in the ‘pharmacophore’. Effects analysis of 14 mutants in the predicted functional domains of ANEP on mouse twisting models showed that the analgesic activity of mutants L15 and E24 of the ‘pharmacophore’, W36, T37, W38, and T39 forming the loop between the β2- and β3-strands and N8, V12, C60, and K64 in the NC domain increased distinctly after these residues were substituted for Ala, respectively. The binding modes and the active sites predicted were consistent with available mutagenesis data, and which is meaningful to understand the related mechanisms of ANEP for Na_v1.7. Full article

(This article belongs to the Special Issue Scorpion Toxins)

► Show Figures

Figure 1

1908 KiB

Open AccessArticle

Tityus serrulatus Scorpion Venom: In Vitro Tests and Their Correlation with In Vivo Lethal Dose Assay

by Daniela Cajado-Carvalho, Juliana Galvão, Alexandre K. Kuniyoshi, Patrícia Dos Santos Carneiro, Adriana Franco Paes Leme, Bianca Alves Pauletti, Eliana Blini Marengo and Fernanda V. Portaro

Toxins 2017, 9(12), 380; https://doi.org/10.3390/toxins9120380 - 23 Nov 2017

Cited by 6 | Viewed by 6619

Abstract

Scorpion stings are the main cause of human envenomation in Brazil and, for the treatment of victims, the World Health Organization (WHO) recommends the use of antivenoms. The first step to achieve effective antivenom is to use a good quality venom pool and to evaluate it, with LD₅₀ determination as the most accepted procedure. It is, however, time-consuming and requires advanced technical training. Further, there are significant ethical concerns regarding the number of animals required for testing. Hence, we investigated the correspondence between LD₅₀ results, in vitro assays, and a strong correlation with proteolytic activity levels was observed, showing, remarkably, that proteases are potential toxicity markers for Tityus serrulatus venom. The comparison of reversed-phase chromatographic profiles also has a potential application in venoms’ quality control, as there were fewer neurotoxins detected in the venom with high LD₅₀ value. These results were confirmed by mass spectrometry analysis. Therefore, these methods could precede the LD₅₀ assay to evaluate the venom excellence by discriminating—and discarding—poor-quality batches, and, consequently, with a positive impact on the number of animals used. Notably, proposed assays are fast and inexpensive, being technically and economically feasible in Tityus serrulatus venom quality control to produce effective antivenoms. Full article

(This article belongs to the Special Issue Scorpion Toxins)

► Show Figures

Figure 1

292 KiB

Open AccessArticle

Target-Specificity in Scorpions; Comparing Lethality of Scorpion Venoms across Arthropods and Vertebrates

by Arie Van der Meijden, Bjørn Koch, Tom Van der Valk, Leidy J. Vargas-Muñoz and Sebastian Estrada-Gómez

Toxins 2017, 9(10), 312; https://doi.org/10.3390/toxins9100312 - 4 Oct 2017

Cited by 18 | Viewed by 6977

Abstract

Scorpions use their venom in defensive situations as well as for subduing prey. Since some species of scorpion use their venom more in defensive situations than others, this may have led to selection for differences in effectiveness in defensive situations. Here, we compared the LD₅₀ of the venom of 10 species of scorpions on five different species of target organisms; two insects and three vertebrates. We found little correlation between the target species in the efficacy of the different scorpion venoms. Only the two insects showed a positive correlation, indicating that they responded similarly to the panel of scorpion venoms. We discuss the lack of positive correlation between the vertebrate target species in the light of their evolution and development. When comparing the responses of the target systems to individual scorpion venoms pairwise, we found that closely related scorpion species tend to elicit a similar response pattern across the target species. This was further reflected in a significant phylogenetic signal across the scorpion phylogeny for the LD₅₀ in mice and in zebrafish. We also provide the first mouse LD₅₀ value for Grosphus grandidieri. Full article

Journal Menu

Journal Browser

Scorpion Toxins

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (10 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI